Di Clemente, L. et al. Interictal habituation deficit of the nociceptive blink reflex: an endophenotypic marker for presymptomatic migraine? Brain 130, 765-770

Headache Research Unit, University Department of Neurology, University of Liège, Liège, Belgium.
Brain (Impact Factor: 9.2). 04/2007; 130(Pt 3):765-70. DOI: 10.1093/brain/awl351
Source: PubMed


Habituation of the nociception-specific blink reflex (nBR) is reduced interictally in migraine patients. This could be related to the habituation deficit of evoked cortical responses, a reproducible abnormality in migraine which has a familial character, or to central trigeminal sensitization due to repeated attacks. We compared nBR habituation in healthy volunteers devoid of personal or family history of migraine (HV), in migraine without aura patients (MO) and in healthy volunteers with a family history of migraine in first degree relatives (HV-F). We elicited the nBR by stimulating the right supraorbital region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F. Habituation was measured as the percentage area-under-the-curve decrease in 10 consecutive blocks of five averaged rectified responses. nBR habituation was clearly reduced in MO and HV-F compared to HV. Percentage area under the curve decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P = 0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality with potentiation instead of habituation in the second block. We found a positive intraindividual correlation between attack frequency and habituation in MO (r = 0.621; P = 0.010). Migraine patients have interictally a deficient habituation of the nBR which is inversely related to attack frequency, suggesting that it is not due to trigeminal sensitization. Surprisingly, the most pronounced habituation deficit is found in asymptomatic individuals with a family history of migraine. Deficient nBR habituation could thus be a trait marker for the genetic predisposition to migraine.

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    • "Interestingly, the nBR does not behave differently from controls in cluster headache in terms of habituation[36], although there is certainly lateralized facilitation[37]. The observation of an interictal persistent change raises the possibility of an endophenotypic marker for migraine[33]. This is important when one considers migraine as a substantially centrally mediated genetic disorder[8]. "
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    ABSTRACT: Background: The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments. Methods: The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 μg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, μV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed. Results: There was an effect due to DRUG on the ipsilateral (F3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions. Conclusion: Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any μ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.
    Full-text · Article · Dec 2015 · The Journal of Headache and Pain
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    • "We recorded 16 rectified EMG responses that were averaged off-line. As previously described, the first response of each nBR recording session was excluded from the signal analysis to avoid contamination with startle responses [30], [31], [32]. The remaining 15 sweeps were averaged in 3 sequential blocks of 5 responses. "
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    ABSTRACT: Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not known. To address this issue in healthy human subjects we modulated differentially visual cortex activity by repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation, and studied the effect on supraorbital pain thresholds and the nociceptive-specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi- and contralaterally and potentiated habituation contralaterally. After high frequency or sham rTMS over the visual cortex, and rMS over the right greater occipital nerve we found no significant change. By contrast, excitatory flash light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi- and contralaterally and increased habituation contralaterally. Our data demonstrate in healthy subjects a functional relation between the visual cortex and the trigeminal nociceptive system, as assessed by the nociceptive blink reflex. The results argue in favour of a top-down inhibitory pathway from the visual areas to trigemino-cervical nociceptors. We postulate that in normal conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of vision by too frequent blinking and that hypoactivity of the visual cortex for pathological reasons may promote headache and photophobia.
    Full-text · Article · Jun 2014 · PLoS ONE
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    • "However, lack of clinical features of migraine or other types of primary headache in FH group suggests that the amplitude asymmetry of blood pulsations indicates less significant deviation from the normal blood supply than the temporal asymmetry, and may probably indicate a predisposition to migraine. Moreover, not all subjects of the FH group are genetically predisposed to migraine [22]. The combination of the two types of asymmetry perhaps is needed to be associated with typical migraine. "
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    Full-text · Article · Dec 2013 · PLoS ONE
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